NIH Funds Designer AIDS Drugs

WASHINGTON—When Donald Armstrong of the Memorial Sloan-Kettering Cancer Center and his collaborators began to search for compounds that could kill the AIDS virus, they took an increasingly popular approach to the development of anti-viral drugs: they designed their own. Since October the National Institutes of Health have spent or set aside about $25 million for projects like Armstrong‘s that take a targeted approach to developing drugs against AIDS. Most extramural funding for the p

By Ron Cowen | March 9, 1987

WASHINGTON—When Donald Armstrong of the Memorial Sloan-Kettering Cancer Center and his collaborators began to search for compounds that could kill the AIDS virus, they took an increasingly popular approach to the development of anti-viral drugs: they designed their own.

Since October the National Institutes of Health have spent or set aside about $25 million for projects like Armstrong‘s that take a targeted approach to developing drugs against AIDS. Most extramural funding for the program—about $13 million—comes from grants administered jointly by the National Cancer Institute and the National Institute of Allergies and Infectious Diseases. It is part of the $252 million that NIH will spend this year on AIDS research.

An additional $10 million, awarded from the director‘s office at NIH, has been divided equally between extramural and intramural research. Applications for the $5 million in extramural funds are being accepted through March 23 by the National Institute of General Medical Sciences for studies of viral structure; the intramural awards are meant to enlist the help of X-ray crystallographers, spectroscopists and other NIH researchers not ordinarily involved in AIDS research.

Advances in molecular biology and in imaging techniques, including two-dimensional magnetic resonance imaging, electron microscopy and computer modeling, have revealed atom-by-atom portraits of viruses and have made it possible to design drugs that attack specific viral structures without harming healthy cells. NIH officials and researchers believe that the program to develop drugs against AIDS will spur the development of drugs to treat other viral diseases, especially those caused by retroviruses.

“Progress in sequencing nucleic acids and the generation of 3-D pictures of proteins has given us the information to inhibit proteins needed for viruses to replicate,” said Ed Rail, NIH deputy director of intramural research. “Viruses are killed, but not normal cells.”

The five investigative teams already awarded grants are headed by Donald Armstrong, Bill Hazeltine at the Dana Farber Cancer Institute, Andre Nahmias at Emory University, Dani Bolognesi at Duke University and Paul Zamecnik at the Worcester Foundation for Experimental Biology. Hazeltine‘s grant—about $700,000 annually for five years—is the largest of the five.

The search for anti-viral and anti-cancer compounds was hit-or-miss before scientists learned how to map the structure of viruses, according to George Galasso, NIH deputy director of extramural research at NIH. “You pulled compounds off the shelf and tested them,” he said. “Sometimes you‘d find a drug active against one disease while looking for something else. If you found the right compound, it was serendipity.”

AZT‘s anti-viral activity against AIDS was discovered after it had been tested for its potential as an anti-cancer drug, Galasso noted, although many researchers continued to believe that the toxicity of anti-viral drugs would outweigh their benefit in fighting viruses. The development of acyclovir and vidarabine to combat two types of herpes has changed many minds, Galasso said, but the Food and Drug Administration still has approved only seven anti-viral drugs.

Many of the grants under the NIH anti-viral drug program are for collaborative efforts, Galasso said. “There aren‘t that many places which have all the talents needed,” he said. Armstrong‘s team includes four laboratories at Sloan-Kettering, a primate laboratory at New York University and scientists at the Centers for Disease Control. Hazeltine‘s research team, which hopes to develop rapid assays to screen “tens of thousands” of compounds for possible anti-AIDS activity, draws on scientists at Columbia University; the Southwest Research Foundation in San Antonio, Tex., which supplies primates; and the, pharmaceutical firm of SmithKline Beckman.

Hazeltine believes the drug development program will require 10 to 15 years of hard work. “Continued support from NIH is absolutely necessary,” he said.